MicroRNA programs in normal and aberrant stem and progenitor cells
MicroRNA programs in normal and aberrant stem and progenitor cells
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DOI：
10.1101/gr.111385.110
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发表时间：
2011-05-01
期刊：
影响因子：
7
通讯作者：
Chen, Chang-Zheng
中科院分区：
文献类型：
--
作者：
Arnold, Christopher P.;Tan, Ruoying;Chen, Chang-Zheng
新的证据表明，microRNA (miRNA) 是一类丰富的类似于 22 核苷酸小调节 RNA 的化合物，在控制干细胞和祖细胞的转录后遗传程序中发挥着关键作用。在这里，我们系统地检查了各种成体组织特异性干细胞及其分化对应物中的 miRNA 表达谱。这些分析揭示了血液、肌肉和神经干细胞群体常见或独特的 miRNA 程序，以及标志着从自我更新和静止干细胞向增殖和分化祖细胞转变的 miRNA 特征。此外，我们还发现了干/祖细胞转变 miRNA (SPT-miRNA) 特征，该特征可以预测遗传扰动对突变干/祖细胞自我更新和增殖潜力的影响，例如 PTEN 和 Rb 家族的丢失、AML1-ETO9a 表达和 MLL-AF10 转化。我们发现一些 SPT-miRNA 控制胚胎干细胞的自我更新和造血干细胞 (HSC) 的重建潜力。最后，我们证明 SPT-miRNA 协调调节已知在控制 HSC 自我更新中发挥作用的基因，例如 Hoxb6 和 Hoxa4。总之，这些分析揭示了可能控制正常和异常干细胞和祖细胞关键过程的 miRNA 程序，为剖析干细胞转录后调控网络奠定了基础。
Emerging evidence suggests that microRNAs (miRNAs), an abundant class of similar to 22-nucleotide small regulatory RNAs, play key roles in controlling the post-transcriptional genetic programs in stem and progenitor cells. Here we systematically examined miRNA expression profiles in various adult tissue-specific stem cells and their differentiated counterparts. These analyses revealed miRNA programs that are common or unique to blood, muscle, and neural stem cell populations and miRNA signatures that mark the transitions from self-renewing and quiescent stem cells to proliferative and differentiating progenitor cells. Moreover, we identified a stem/progenitor transition miRNA (SPT-miRNA) signature that predicts the effects of genetic perturbations, such as loss of PTEN and the Rb family, AML1-ETO9a expression, and MLL-AF10 transformation, on self-renewal and proliferation potentials of mutant stem/progenitor cells. We showed that some of the SPT-miRNAs control the self-renewal of embryonic stem cells and the reconstitution potential of hematopoietic stem cells (HSCs). Finally, we demonstrated that SPT-miRNAs coordinately regulate genes that are known to play roles in controlling HSC self-renewal, such as Hoxb6 and Hoxa4. Together, these analyses reveal the miRNA programs that may control key processes in normal and aberrant stem and progenitor cells, setting the foundations for dissecting post-transcriptional regulatory networks in stem cells.